Association between mammary adipocyte diameter and survival outcomes in breast cancer patients.

e12720 Background: Obesity is associated with poorer breast cancer outcomes, yet body mass index (BMI) has limitations in assessing adiposity and metabolic dysfunction. Mammary adipocyte hypertrophy may better reflect the biological impact of obesity on tumor behavior and breast cancer prognosis. We examined if mammary adipocyte diameter is associated with overall and recurrence-free survival in breast cancer patients, independently of BMI. Methods: Women with newly diagnosed invasive, non-metastatic breast cancer were recruited at the Centre des Maladies du Sein (Quebec, Canada) between 2000-2012. Mean mammary adipocyte diameter (μm) was measured on hematoxylin- and eosin-stained tissue sections located ≥1 cm from the tumor using automated segmentation in ImageJ. Patients were followed through December 31, 2023. Hazard ratios (HR) and 95% confidence intervals (CI) from adjusted multivariate Cox models estimated associations of mean adipocyte diameter (per 10 μm) with overall survival (OS) and recurrence-free survival (RFS). Analyses were also stratified by combined estrogen receptor (ER) and progesterone receptor (PR) status, in line with previous findings in the literature. Results: Among 2,211 women (median follow-up: 13.2 years), mean adipocyte diameter was 75.0 μm (range: 46.3-116.4), and 804 deaths occurred (36.4%) and 1,069 recurrences (48.3%) were observed. In adjusted analyses, each 10 μm increase in adipocyte diameter was associated with poorer OS (HR = 1.08; 95% CI: 1.00-1.17; p = 0.047) particularly among patients whose tumors were ER+/ PR- (HR = 1.25; 95% CI: 1.01-1.55; p = 0.041). However, these associations were attenuated and no longer significant after adjusting for BMI (HR = 1.01; 95% CI: 0.93-1.10; p = 0.80 and HR = 1.10; 95% CI: 0.85-1.41; p = 0.47, respectively). No significant association with RFS was observed, regardless of BMI adjustment. Conclusions: Larger mammary adipocyte diameter was associated with poorer overall survival, specifically in patients with ER+/PR- tumors. While BMI accounted for much of this association, adipocyte size may be related to other clinical outcomes in the cancer care continuum, such as the long-term metabolic effects of cancer treatments. Further research is needed to explore these relationships and their potential value in improving survivorship and tailoring patient care in breast cancer.